Two stories in 360 yesterday – the timing was pure coincidence – have us thinking again about the FDA’s muddled and increasingly untenable position on truthful off-label “promotion” – broadly defined as any accurate information disseminated by an FDA-regulated manufacturer about an  off-label use.  

The first of these articles described the oral argument in Amarin, Inc. v. FDA, a case which we’ve been following closely, here,here, and here.  The Amarin case, which challenges the FDA’s truthful off-label promotion ban under the First Amendment in a Caronia-bound court, saw the FDA in retreat (by letter) before argument, but apparently returning to its old absolutist views at the argument itself.  According to 360:

[The government] advanced an aggressive interpretation of the Caronia decision, arguing that truthful statements alone can still be the basis for enforcement if the government demonstrates that a drug was promoted for unapproved uses that weren’t generally recognized as safe and effective.

Again according to 360’s report, the court appeared torn.  On the one hand, it would be highly unusual to enjoin an FDA prosecution that hasn’t even happened, and there are problems declaring particular medical statements “truthful” when the science is evolving.  On the other hand, the FDA allows exactly the same statements in the context of dietary supplements, and Caroniaholds what it holds – which isn’t at all what the government argued.

Probably the simplest result would be for the court in Amarin to hold that there is currently no evidence that the company’s science has been disproven sufficient to remove the proposed off-label promotion from Caronia’s holding that the First Amendment protects truthful scientific speech.  The 360 article reflects some sparring over this result, with each side trying to put the burden on the other to reopen the issue should the underlying science change.

The second 360 article arises from an editorial recently published in JAMA by three physicians who sat on the FDA advisory panel convened to advise on the approval of flibanserin, a drug sometimes (and rather misleadingly) called “female Viagra.”  This drug, which has a problematic risk/benefit profile leading to two prior failures to obtain FDA approval, has been resubmitted as a treatment for hypoactive sexual desire disorder (“HSDD”).  The manufacturer has better safety/effectiveness data for HSDD, but the testimony at the panel hearing made clear that significant off-label use for purposes of sexual gratification would also occur:

A final concern regarding flibanserin relates to its likely use in clinical practice, and this was a major issue for the committee.  Although there are few reliable estimates of the prevalence of HSDD, the product, as with others, is all but certain to be used off-label among a broader population of women than has been studied, many of whom may not fulfill formal diagnostic criteria for HSDD and many of whom may have conditions or concomitant medication use that increases the risk of adverse events.  The concerns about off-label use were reinforced by public speakers at the meeting who expressed their need for flibanserin, while at the same time reporting conditions that may have excluded them from on-label treatment, such as a cancer diagnosis or postmenopausal status.

Gellad, Flynn & Alexander, “Evaluation of Flibanserin: Science & Advocacy at the FDA” ¶9 (JAMA online July 6, 2015).

Indeed, as 360 also discusses, political advocacy of such off-label uses exists from a group, “Even the Score,” which calls attention to the great disparity between the number of FDA-approved drugs to combat sexual dysfunction in men – 26 – and the lack of any FDA-approved drugs at all to treat the same condition in women. Aside from the political advocacy twist, this is a relatively common off-label issue.  Lots of products are FDA-approved for relatively narrow indications, and then used on a much broader scale, even becoming the standard of care for some or all of those broader uses.  That’s what the Bone Screw litigation was all about, and what the underlying fraud on the FDA allegations inBuckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341 (2001), concerned.  As we've discussed already, drug induced abortion seems to be another, more recent, example.

What these two separate developments – linked only by the existence of off-label use – have in common is the continuing need for the FDA to move away from rigid, speech-based regulation of off-label promotion and instead adopt more constitutionally sound procedures to address off-label promotion. To us, the obvious solution to both of these situations is for the FDA not to ban truthful promotion or to reject drugs that meet approval criteria for fear of widespread off-label use.  The FDA should be able to require manufacturers to monitor off-label use, either specific uses that concern the Agency, or more generally. Then, if the level of off-label use of a particular product reaches frequency/ubiquity criteria set by the FDA after formal rulemaking, the FDA should have the power to mandate that the safety and effectiveness of the off-label use be formally studied, whether it’s being promoted for those off-label uses or not.

We’ve made the same proposal before, both in the blog and in amicus briefs asserting less restrictive alternatives to the FDA’s ban on truthful off-label promotion.  Requiring companies to monitor off-label use and submit statistics to the FDA does not implicate the First Amendment.  Nor does setting criteria for when the scale of off-label use is such that formal studies are both advisable from a public health standpoint, and economically feasible given the size of the market.  The two stories we saw yesterday, concerning the Amarin case and flibanserin provide specific examples of situations where a First Amendment-compliant approach to speech involving off-label uses would, in fact, be more beneficial than the FDA’s current prohibitions against truthful speech.